Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000803734 | SCV000943619 | uncertain significance | Charcot-Marie-Tooth Neuropathy X | 2018-11-28 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 70 of the GJB1 protein (p.Pro70Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Charcot-Marie-Tooth disease (PMID: 18636082, Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Pro70 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID:10873293, 21692908), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Inherited Neuropathy Consortium | RCV000789863 | SCV000929248 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |